Self-maintaining CD103þ cancer-specific T cells are highly energetic with rapid cytotoxic and effector responses

Abstract

Enrichment of CD103þ tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103þ cytotoxic CD8þ T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103þ CTLs by assessing T-cell receptor (TCR)–matched CD103þ and CD103– cancer-specific CTL immunity in vitro and its immunophenotype ex vivo. Interestingly, we found that differentiated CD103þ cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103þ CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103þ cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.